Toxicity profile of chemotherapy agents used in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies.

INTRODUCTION: Morbidity associated with cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is due to the synergistic effect of cytoreduction, effect hyperthermia and the cytotoxic agents used for HIPEC. This study was done to analyse the postoperative morbidity in relation to the chemotherapy agent used in patients undergoing CRS-HIPEC for peritoneal surface malignancy (PSM) in Indian set up. MATERIALS AND METHODS: Patient with PSM, underwent CRS-HIPEC as per the institutional protocol. Patients were stratified as per the chemotherapy drug used during HIPEC & perioperative outcome were documented. RESULTS: 163 patients underwent CRS-HIPEC for PSM: 67.4% were of ovarian primary. Others were colorectal, appendicular, gastric primary and rare tumors.Cisplatin was the most common drug used: as alone (57.05%) or in combination with Adriamycin (12.88%). Mitomycin-C (MMC) was used in 20% and oxaliplatin in 10%.Grade 3-5 morbidity in the whole cohort was 44.8% and grade 1-2 was 74%.Grade 1-2 electrolyte abnormality was the most common morbidity overall and grade 3-4 hematological toxicity was the most common severe morbidity. Frequency of grade 3-5 morbidity were 38.7%, 48.5%,50% and 61.9% for Cisplatin alone, MMC, oxaliplatin and Adriamycin + cisplatin respectively. None of the patients had grade 3-4 nephrotoxicity as sole complication. All major complications were highest in the group who received Adriamycin. Cisplatin was associated with higher rate of electrolyte imbalance, oxaliplatin with post-operative bleeding. Rates of other complications did not differ significantly. CONCLUSION: Cisplatin followed by MMC were the well tolerated drugs during HIPEC and tolerance to Adriamycin combination regimen in Indian patients was poor.

Hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies: A single institution Indian experience.

BACKGROUND: Cytoreductive surgery followed by hyper- thermic intraperitoneal chemotherapy (HIPEC) has shown better oncological outcomes in peritoneal surface malignancies (PSM). We assessed the feasibility and perioperative outcomes of this procedure in Indian patients. METHODS: In this prospective observational study from February 2013 to April 2015, we included 56 patients (41 females, 73.2%) with PSM. They had a good performance status, were either treatment-naïve or previously treated by surgery and systemic chemotherapy. They underwent cytoreductive surgery followed by HIPEC using a hyperthermia pump, with the temperature at 42 °C for 30-90 minutes. The chemotherapy regimen was based on the primary malignancy. Perioperative outcome data were collected and analysed. We also analysed the short-term oncological outcomes. RESULTS: Our patients included those with peritoneum confined ovarian carcinoma (32, 57.1%), colorectal carcinoma (9, 16.1%), pseudomyxoma peritonei (7, 12.5%), meso- thelioma (2, 3.6%), gastric carcinoma (2, 3.6%) and others (4, 7.1%). The median duration of surgery including HIPEC was 9 hours and the median hospital stay was 12 days. The median time for gastrointestinal recovery was 5 days. One-fifth of patients (11, 19.7%) required an extended stay in the inten- sive care unit. The most common grades 3 and 4 complications were hypocalcaemia 32.1%, hypokalaemia 32.1%, anaemia 21.4% and thrombocytopenia 7.1%. Major morbidity requiring surgical intervention occurred in 8.9% of patients. The 60-day operative mortality was 1.8%. At a median follow-up of 16 months, 7.1% developed peritoneal recurrence, 8.9% had systemic recurrence and 7.1% succumbed to the disease. Patients with platinum-resistant ovarian carcinomas had more peritoneal recurrence (3.6%). CONCLUSION: In patients with PSM, surgical cytoreduction and HIPEC is feasible and potentially beneficial. It can be done with low mortality and acceptable morbidity. It requires a dedicated team of surgeons, anaesthetists and intensivists and proper infrastructure.